Smoking remains a major public health problem, contributing to the death of millions of people worldwide every year. Greater understanding of the mechanisms that drive smoking behavior is needed to prevent additional people from becoming tobacco dependent and improve treatment for current smokers. To date, most research has focused on the primary reinforcing effects of nicotine. However, current evidence suggests that non-nicotine factors, including the sensorimotor stimuli associated with nicotine delivery, are also important. Animal research has shown that nicotine-associated stimuli potentiate acquisition, support maintenance, retard extinction, and facilitate reacquisition of nicotine self-administration. Similarly, human experimental work has demonstrated that smoking stimuli determine, to a large extent, smoking satisfaction, relief from withdrawal and craving, and smoking reinforcement. However, the effects of smoking stimuli have, almost exclusively, been studied during brief, laboratory sessions. The specific aims of this proposal are to assess the positive subjective, craving-reducing, withdrawal attenuating and reinforcing effects of smoking stimuli in the absence of nicotine, and to determine whether these effects dissipate during an extended period of exposure. The proposed study will compare the effects of smoking denicotinized, smoking nicotine containing cigarettes and not smoking, in a randomized, between-subjects, inpatient design. Participants will reside for twelve nights at the Johns Hopkins Bayview General Clinical Research Center. During this time, combinations of unrestricted smoking, subjective measures of both the positive effects of smoking and withdrawal-relief, sleep recordings, and controlled laboratory assessments of smoking effects, smoking topography and smoking reinforcement will be employed. The results are likely to extend current knowledge of 1) the mechanisms maintaining smoking behavior, 2) non-nicotine, factors promoting smoking during abstinence from nicotine, and 3) changes in the effects of smoking stimuli following repeated exposures. This knowledge will help clarify the treatment needs of smokers trying to achieve abstinence from tobacco. If the reinforcing effects of smoking stimuli prove to be important determinants of smoking behavior, current focus on nicotine alone is inadequate. Novel treatment strategies (e.g., extinction or sensorimotor stimulation replacement therapies), that specifically address the sensorimotor effects of smoking, would be warranted.